IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
artículos
Título:
Involvement of mitochondriañ ATP-sensitive potasium channel in the beneFIcial effects of fasting on tge ischemic reperfused rat heart
Autor/es:
M. G. MARINA PRENDES; M. S. GONZÁLEZ; R. HERMANN; N. G. PASCALE; M. E. TORRESÍN; M. M. JAITOVICH; E. A. SAVINO; A. VARELA
Revista:
World Heart Journal
Editorial:
Nova Science Poblishers
Referencias:
Año: 2009 vol. 2 p. 9 - 16
ISSN:
1556-4002
Resumen:
SUMMARY      1.Fasting improves contractile recovery and attenuates lactate production and mitochondrial permeability transition (MPT) without altering cell viability in ischaemic-reperfused rat hearts. 5-hydroxydecanoate (5-HD), a mitochondrial ATP-sensitive K+ channel (K-ATPmito) blocker, abolishes the improvement of mechanical recovery elicited by fasting despite it decreases lactate production, suggesting that K-ATPmito might be involved in the preservation of contractility. This study aimed to explore the contribution of K-ATPmito in the attenuation of MPT which in turn may improve mitochondrial energetics.    2.Langendorff-perfused hearts from fed and fasted rats were subjected to ischaemia-reperfusion in the presence or absence of 5-HD. To assess whether 5-HD has any direct effect on glycolysis, a cell free heart extract containing all the glycolytic enzymes was used. MPT was quantitated measuring the mitochondrial 2-[3H]-deoxyglucose (3H-2-DG) entrapment. Total heart 3H-2-DG  content as an estimation of necrosis was measured. As an index of mitochondrial energetic function, the rate of ATP synthesis was examined in mitochondria isolated from the ischaemic-reperfused hearts.    3. Fasting increased the rate of mitochondrial ATP synthesis and attenuated MPT. 5-HD abolished these protective effects. 5-HD did not change total heart 3H-2-DG content indicating that it lacked effects on cell survival. Since 5-HD did not affect glucose consumption and lactate production in the cell-free heart-extract the inhibition of glycolysis could be due to its own oxidative metabolism.    4. It may be concluded that cardioprotection elicited by fasting in the ischaemic-reperfused heart could be ascribed, at least in part, to the K-ATPmito activation whichin turn inhibits MPT and induces energetic preservation.      Key words: 5-hydroxydecanoate, mitochondrial permeability transition, ATP